1690-P: PG-110, a Novel Bispecific Antibody Targeting ActRII and Myostatin, Enhances Fat-Specific Weight Loss and Improves Bone Health in Combination with GLP-1 Agonist Therapy

Introduction and Objective: Incretin-based drugs effectively induce weight loss but often lead to unintended reductions in muscle mass and bone density, both crucial for metabolic health and physical function. To address this limitation, we investigated the combination of semaglutide with PG-110, a novel bispecific antibody targeting ActRII and myostatin, in a diet-induced obese (DIO) mouse model. Methods: Diet-induced obese C57BL6/N mice were treated with semaglutide (QD) and PG-110 (QW) for two weeks. Body weight and composition were measured to assess the effects on fat mass, muscle mass, and bone mineral density (BMD). Results: Semaglutide alone effectively reduced body weight. When combined with PG-110, fat mass loss was significantly enhanced, and the rate of overall weight loss accelerated, with no significant changes observed in lean mass. Furthermore, PG-110 treatment markedly increased hind limb BMD. Conclusion: The combination of semaglutide and PG-110 synergistically enhances fat-specific weight loss and improves BMD in DIO mice without negatively affecting lean mass. These findings suggest that PG-110 may offer a promising therapeutic strategy to optimize fat loss and skeletal health when used in combination with incretin-based therapies. Disclosure Y. Son: None. S. Lee: None. J. Kim: None. S. Yang: None. Y. Sung: None.